Fumaric Acid Ester Metabolites act as a regulator of the micro RNA MIR-21, which is necessary to create the brain-homing T cells that are active in multiple sclerosis. Carter Eitreim

Understanding and mitigating the role of epigenetics (environmental influences that trigger changes in gene expression) in disease development is a major goal of researchers. Now, a newly published paper featured on the March cover of the journal Brain adds significantly to this work by detailing how metabolites can be used to inhibit epigenetic mechanisms and effectively treat a range of diseases, including multiple sclerosis (MS).

Dimethyl fumarate (Tecfidera™)–a cell-permeable metabolite in the family of fumaric acid esters (FAEs)–is an approved treatment for MS and is potentially an effective therapy for other autoimmune diseases. The precise mechanism of the drug’s action has been only partially understood, however. In their new paper, researchers at the Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New York and the Icahn School of Medicine at Mount Sinai take a major step toward unraveling the mystery by identifying a possible mechanism of action for FAEs. In doing so, they also highlight new concepts that may lay the groundwork for the development of novel classes of drugs for the treatment of MS and other diseases.

Scientists believe that MS develops when epigenetic changes cause certain brain-homing immune cells–or T cells–to attack the central nervous system. In their current paper, researchers posited that FAE metabolites work by mitigating the development of certain brain-homing T cells.

“This work has given us extremely useful insight into how we might leverage the metabolic-epigenetic interplay between cells and their environment to create new immune-modulating therapies for diseases like MS,” said Patrizia Casaccia, director of the ASRC Neuroscience Initiative and a professor of genetics and neuroscience at Mount Sinai. “It may one day be possible to target and suppress production of the specific brain-homing T cells that play a role in the development of MS.”